Mutual recognition, binding and consequent triggering of second messenger events depends upon the complementarity of the conformations and internal motions of both the neuropeptides and their receptors in the target cell membranes. We will approach the investigation of this key area by total analysis of the side chain proton magnetic resonance spectra of the neuropeptides and the selected agonists and antagonists, principally by the methods of double resonance, difference nmr, and synthesis of isotopically labelled peptides. This information will be used to produce a dynamic (not static) interpretation of neuropeptide conformation and of neuropeptide-receptor and neuropeptide-protease interactions, and to design improving neuropeptide analogs. Specific neuropeptides to be studied include (a) the enkephalins which are important for understanding the biochemical events associated with morphine addiction and as possible analgesia (euphorigens) and neurotransmitters, (b) oxytocins and MSH, which have importance in physiology learning and behavior, and (c) lipotropin, the putuitary precursor of beta MSH and enkephalins. Two related programs will be started: (a) isolation and characterization of the neuroproteases which cleave lipotropin to enkephalin and (b) 31P NMR will be explored as a technique for comparing phosphometabolite level in whole liver, hepatocytes, homogenates, mitochondria and other liver fractions. This is a collaborative effort and could lead to the study of peptide hormone effects on whole tissue by NMR, a nondestructive method.